The aims of the proposed studies are to evaluate the extent of neurobehavioral toxicity in rabbits following prolonged exposure to aluminum. Rabbits will be exposed in utero; neonatally, via lactation; as immature rabbits, by peripheral administration; and as adults, including pregnant and lactating adults, by peripheral administration. The neurobvehavioral toxicity will be quantitated using behavioral analytical, and histapathological methods developed with support from an ADAMHA small grant. The rate of acquisition of a classically conditioned reflex (nictitating membrane response) and the retention of the learned behavior will be determined. The levels of aluminum in various peripheral tissues and specific brain regions will be determined using flameless atomic absorption spectroscopy. The extent of neurofibrillary tangles within cell bodies and proximal neuronal processes will be assessed using the Bielschowsky silver stain for neuronal fibrils. Comparisons will be made among the exposed and control subjects to determine the relative risk of aluminum toxicity from exposure at the stages of development testing and to determine if there is any protective effect of pregnancy or lactation. These studies should suggest the relative resk to people of various ages in our society from increased exposure to aluminum. As we are exposed to more aluminum in our immediate environment (from solubilization by acid rain and the burning of coal), in our food and water, and from the many other sources of aluminum we produce and consume, the concern for hazard from exposure increases. The results from the proposed studies should further our understanding of the interaction between aluminum and some of those biological factors which seem to contribute to aluminum associated diseases such as dialysis encephalopathy and Alzheimer's disease.